Analysis of regulatory mechanisms of newly identified ERK substrates

• Project/Area Number: 23570231
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: The University of Tokushima
• Principal Investigator: KOSAKO Hidetaka 徳島大学, 藤井節郎記念医科学センター, 教授 (10291171)
• Co-Investigator(Renkei-kenkyūsha): SAITOH Hisato 熊本大学, 大学院自然科学研究科, 教授 (50211925) ; TSUMOTO Kouhei 東京大学, 大学院工学系研究科, 教授 (90271866)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ERK / MAPキナーゼ / リン酸化 / 細胞内情報伝達 / 細胞運動 / 抗リン酸化抗体 / プロテオーム / ダイニン / 細胞接着 / 細胞間接着 / 糸球体 / がん化

Outline of Final Research Achievements

ERK/MAP kinase is evolutionally conserved in eukaryotes and plays multiple and important roles in cells by phosphorylating various substrates. We have recently identified new ERK substrates by developing a phosphoproteomic approach. In this study, we identified phosphorylation sites of several of these ERK substrates and biochemically analyzed phosphorylation-dependent regulation of their functions. Furthermore, each ERK substrate was shown to be involved in ERK-mediated regulation of cellular functions.

Research Products

• [Journal Article] Ubiquitin is phosphorylated by PINK1 to activate parkin. (2014)
  • Author(s): Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., Endo, T., Fon. E. A., Trempe, J. F., Saeki, Y., Tanaka, K., and Matsuda, N.
  • Journal Title: Nature Volume: 510(in press) Issue: 7503 Pages: 162-166
  • DOI: 10.1038/nature13392
  • Peer Reviewed
• [Journal Article] Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells (2014)
  • Author(s): Haruko Tsurumi, et. al
  • Journal Title: Kidney International Volume: Epub Issue: 3 Pages: 548-557
  • DOI: 10.1038/ki.2014.85
  • Peer Reviewed / Open Access
• [Journal Article] Parkin catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation (2013)
  • Author(s): Masahiro Iguchi, Yuki Kujuro, Kei Okatsu, Fumika Koyano, Hidetaka Kosako, Mayumi Kimura, Norihiro Suzuki, Shinichiro Uchiyama, Keiji Tanaka, Noriyuki Matsuda
  • Journal Title: The Journal of Biological Chemistry Volume: 288 Issue: 30 Pages: 22019-32
  • DOI: 10.1074/jbc.m113.467530
  • Peer Reviewed
• [Journal Article] GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance (2013)
  • Author(s): Nakaya M, Tajima M, Kosako H, Nakaya T, Hashimoto A, Watari K, Nishihara H, Ohba M, Komiya S, Tani N, Nishida M, Taniguchi H, Sato Y, Matsumoto M, Tsuda M, Kuroda M, Inoue K, Kurose H
  • Journal Title: Nature Commun Volume: 4 Issue: 1 Pages: 1532-1532
  • DOI: 10.1038/ncomms2540
  • Peer Reviewed
• [Journal Article] PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria (2012)
  • Author(s): 尾勝圭
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1016-1016
  • DOI: 10.1038/ncomms2016
  • Peer Reviewed
• [Journal Article] リン酸化プロテオミクスによるキナーゼ基質の大規模解析 (2011)
  • Author(s): 小迫 英尊
  • Journal Title: 生化学 Volume: 83 Pages: 1122-1127
  • NAID: 10030345967
  • Peer Reviewed
• [Presentation] Identification and Functional Analysis of Protein Kinase Substrates using Various Proteomic Technologies, (2015)
  • Author(s): 小迫 英尊
  • Organizer: Keystone Symposia
  • Place of Presentation: Colorado, USA
  • Year and Date: 2015-01-13
• [Presentation] リン酸化プロテオミクスによるキナーゼ基質の同定と機能解析 (2014)
  • Author(s): 小迫 英尊
  • Organizer: 日本プロテオーム学会2014年会
  • Place of Presentation: つくば国際会議場（茨城県つくば市）
  • Year and Date: 2014-07-17
  • Invited
• [Presentation] リン酸化プロテオミクスを用いたキナーゼターゲットの同定と機能解析
  • Author(s): 小迫英尊
  • Organizer: 愛媛大学JHUPO第２回サテライトジョイントシンポジウム
  • Place of Presentation: 愛媛大学総合情報メディアセンター（愛媛県松山市）
  • Invited
• [Presentation] 蛍光標識二次元ディファレンスゲル電気泳動2D-DIGEから得られた知見と展望.
  • Author(s): 小迫英尊
  • Organizer: 第63回日本電気泳動学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県）
  • Invited
• [Presentation] Multisite phosphorylation of FG nucleoporins by MAP kinases is involved in the regulation of nucleocytoplasmic transport.
  • Author(s): H. Kosako et al.
  • Organizer: Cold Spring Harbor Laboratory Meeting "Dynamic Organization of Nuclear Function"
  • Place of Presentation: Cold Spring Harbor Laboratory (米国ニューヨーク州)
• [Presentation] リン酸化プロテオミクスを用いたキナーゼターゲットの同定と機能解析
  • Author(s): 小迫英尊
  • Organizer: 第2回JHUPOサテライトジョイントシンポジウム
  • Place of Presentation: 愛媛大学総合情報メディアセンター（愛媛県）
  • Invited
• [Remarks] 細胞情報学分野 :: 藤井節郎記念医科学センター
  • URL: http://www.fujii.tokushima-u.ac.jp/cellsignaling/
• [Remarks] 細胞情報学分野｜徳島大学
  • URL: http://www.tokushima-u.ac.jp/fujii/research/cytology/